Evidence of gene-environment interaction for two genes on chromosome 4 and environmental tobacco smoke in controlling the risk of nonsyndromic cleft palate

Wu, T and Schwender, H and Ruczinski, I and Murray, JC and Marazita, ML and Munger, RG and Hetmanski, JB and Parker, MM and Wang, P and Murray, T and Taub, M and Li, S and Redett, RJ and Fallin, MD and Liang, KY and Wu-Chou, YH and Chong, SS and Yeow, V and Ye, X and Wang, H and Huang, S and Jabs, EW and Shi, B and Wilcox, AJ and Jee, SH and Scott, AF and Beaty, TH (2014) Evidence of gene-environment interaction for two genes on chromosome 4 and environmental tobacco smoke in controlling the risk of nonsyndromic cleft palate. PLoS ONE, 9 (2).

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Abstract

Nonsyndromic cleft palate (CP) is one of the most common human birth defects and both genetic and environmental risk factors contribute to its etiology. We conducted a genome-wide association study (GWAS) using 550 CP case-parent trios ascertained in an international consortium. Stratified analysis among trios with different ancestries was performed to test for GxE interactions with common maternal exposures using conditional logistic regression models. While no single nucleotide polymorphism (SNP) achieved genome-wide significance when considered alone, markers in SLC2A9 and the neighboring WDR1 on chromosome 4p16.1 gave suggestive evidence of gene-environment interaction with environmental tobacco smoke (ETS) among 259 Asian trios when the models included a term for GxE interaction. Multiple SNPs in these two genes were associated with increased risk of nonsyndromic CP if the mother was exposed to ETS during the peri-conceptual period (3 months prior to conception through the first trimester). When maternal ETS was considered, fifteen of 135 SNPs mapping to SLC2A9 and 9 of 59 SNPs in WDR1 gave P values approaching genome-wide significance (10-6<P<10-4) in a test for GxETS interaction. SNPs rs3733585 and rs12508991 in SLC2A9 yielded P = 2.26×10-7 in a test for GxETS interaction. SNPs rs6820756 and rs7699512 in WDR1 also yielded P = 1.79×10-7 and P = 1.98×10-7 in a 1 df test for GxE interaction. Although further replication studies are critical to confirming these findings, these results illustrate how genetic associations for nonsyndromic CP can be missed if potential GxE interaction is not taken into account, and this study suggest SLC2A9 and WDR1 should be considered as candidate genes for CP. © 2014 Wu et al.

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Details

Item Type:	Article
Status:	Published
Creators/Authors:	Creators Email Pitt Username ORCID Wu, T Schwender, H Ruczinski, I Murray, JC Marazita, ML marazita@pitt.edu MARAZITA Munger, RG Hetmanski, JB Parker, MM Wang, P Murray, T Taub, M Li, S Redett, RJ Fallin, MD Liang, KY Wu-Chou, YH Chong, SS Yeow, V Ye, X Wang, H Huang, S Jabs, EW Shi, B Wilcox, AJ Jee, SH Scott, AF Beaty, TH
Contributors:	Contribution Contributors Name Email Pitt Username ORCID Editor Pajewski, Nicholas M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
Centers:	Other Centers, Institutes, Offices, or Units > Center for Craniofacial and Dental Genetics
Date:	6 February 2014
Date Type:	Publication
Journal or Publication Title:	PLoS ONE
Volume:	9
Number:	2
DOI or Unique Handle:	10.1371/journal.pone.0088088
Schools and Programs:	School of Dental Medicine > Dental Science
Refereed:	Yes
Date Deposited:	19 Jun 2014 17:13
Last Modified:	22 Jun 2021 13:56
URI:	http://d-scholarship.pitt.edu/id/eprint/21903

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